EARLY antibiotic discontinuation in febrile neutropenia reduced antibiotic exposure without increasing severe outcomes in interim trial findings.
Findings from the ongoing END (Early Neutropenic Fever De-escalation of Antibiotics) study, presented at IDWeek 2026, suggest that stopping empiric antibiotics before bone marrow recovery may be a safe alternative to prolonged treatment in selected patients with hematologic malignancies.
Current guidelines recommend continuing broad-spectrum antibiotics in patients with high-risk febrile neutropenia until bone marrow recovery when no bacterial source is identified. However, prolonged antibiotic exposure can contribute to multidrug resistance, Clostridioides difficile infection, and microbiome disruption, potentially worsening outcomes following cellular therapy.
The Phase IV, open-label, randomized controlled trial is evaluating whether earlier antibiotic discontinuation can reduce unnecessary treatment without compromising patient safety.
Conducted at a single cancer center, the study enrolled adults with hematologic malignancies hospitalized with high-risk febrile neutropenia and no identified bacterial source after 48 hours without fever.
Participants were randomized equally to early discontinuation of empiric intravenous antibiotics or continued treatment until blood count recovery. The prespecified interim analysis assessed severe outcomes, including death, septic shock, and intensive care unit transfer by Day 60, alongside antibiotic exposure.
Between May 2024 and April 2026, 157 participants were randomized, with 148 completing follow-up. Of these, 73 received early antibiotic discontinuation and 75 received standard care.
Severe event rates were comparable between groups, occurring in 11.0% of patients receiving early discontinuation and 13.3% receiving standard care.
Grade 3 or higher adverse events were also similar, while median hospital length of stay was identical at 25 days in both groups.
However, antibiotic exposure differed substantially. Patients in the early discontinuation group experienced a mean of 10.5 antibiotic-free days during neutropenia, compared with 3.8 days in the standard-care group.
This represented 59.4% of neutropenic days without antibiotics in the early discontinuation group, compared with 30.2% under standard care.
These findings suggest that early discontinuation of empiric antibiotics may reduce treatment exposure in selected patients with high-risk febrile neutropenia without an apparent increase in severe clinical outcomes.
However, the results are preliminary, and the trial remains ongoing. Final analyses will be needed to establish whether early antibiotic discontinuation can safely inform broader clinical practice.
Reference
Hannaford A et al. END (Early Neutropenic Fever De-escalation of) Antibiotics Study: an open-label, randomized, controlled phase 4 trial. IDWeek, October 21–24, 2026.
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